Lowering of blood pressure by direct- and indirect-acting serotonin agonists in spontaneously hypertensive rats.

1-(m-Trifluoromethylphenyl)piperazine, a serotonin agonist, lowered blood pressure in spontaneously hypertensive rats (SHR) at doses of 2 to 10 mg/kg s.c. A structurally related compound lacking serotonin agonist activity, 4-(m-trifluoromethylphenyl)piperidine, was ineffective. Quipazine, another serotonin agonist, lowered blood pressure in SHR at doses of 0.1 to 2 mg/kg s.c. Fenfluramine, a serotonin-releasing drug, lowered blood pressure in SHR at doses of 2 and 5 mg/kg s.c. Metergoline (3 mg/kg s.c.), a serotonin antagonist, elevated blood pressure and prevented the decrease by all of the above agents. These findings are consistent with the view that enhancement of central serotonergic function lowers blood pressure in SHR.